The formation of the postsynaptic specialization that receives neurotransmitter from the presynaptic axon is fairly well characterized. However, the formation of the presynaptic specialization that allows for regulated release of neurotransmitter is largely unknown. Neurotransmitter release is achieved through synaptic vesicle fusion with the plasma membrane and is a highly regulated process. Many of the proteins that make up the presynaptic specialization called the active zone play a key role in this regulation. However, the molecular basis of how the active zone is formed is largely unknown. A key question to active zone assembly is how proteins target to this protein rich region. In order to address this question my research proposal will focus on the targeting mechanisms of the active zone protein RIM (for rab3 interacting molecule). Interestingly, we have found that a distinct domain of RIM, which is present in other active zone proteins, is required for proper RIM localization at the active zone. My studies will determine through both genetics and biochemistry the reason this domain is needed for RIM targeting to the active zone, The targeting domain of RIM may prove to be a general targeting mechanism for many active zone proteins.